title: Endogenous angiotensin II contributes to basal peripheral vascular tone in sodium deplete but not sodium replete man.
abstract: OBJECTIVE
  Both endothelin-1 and nitric oxide make important contributions to the maintenance of basal peripheral arteriolar tone. However, the role of angiotensin II, a key hormone regulating cardiovascular and renal function, in the regulation of peripheral vascular tone has not been fully characterised.
  
  
  METHODS
  Using local intra-arterial administration of losartan, a selective angiotensin II type 1 (AT1) receptor antagonist, we examined the contribution of endogenous angiotensin II to the maintenance of basal and sympathetically stimulated vascular tone in the forearm of healthy man under conditions of sodium repletion and depletion. The effects of losartan on responses to exogenous angiotensin I, angiotensin II, bradykinin and noradrenaline were also determined.
  
  
  RESULTS
  Losartan, in keeping with its actions as a selective AT1 receptor antagonist, inhibited responses to angiotensin I and II, but had no effect on responses to bradykinin or noradrenaline. The dose of angiotensin II required to cause a 20% vasoconstriction was 40- and 250-fold greater with 30 and 300 micrograms/min of losartan, respectively. However, in sodium replete subjects, losartan alone caused no significant changes in basal forearm blood flow (95% confidence interval of -7.2 to +8.0%), forearm vascular resistance or sympathetically stimulated forearm vasoconstriction. Sodium depletion elevated plasma renin activity and angiotensin II concentrations (p < or = 0.002) after which acute local administration of losartan increased forearm blood flow in a dose dependent manner (maximum of 69 +/- 17%; p < 0.001).
  
  
  CONCLUSIONS
  Endogenous angiotensin II does not contribute to the acute local maintenance of basal peripheral vascular tone in healthy man except under conditions of renin-angiotensin system activation such as sodium depletion.
authors.affiliation: Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, UK. d.e.newby@ed.ac.uk
authors.forename: D E
authors.initials: DE
authors.lastname: Newby
authors.forename: S
authors.initials: S
authors.lastname: Masumori
authors.forename: N R
authors.initials: NR
authors.lastname: Johnston
authors.forename: N A
authors.initials: NA
authors.lastname: Boon
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001808:Blood Vessels / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008150:Lower Body Negative Pressure; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012964:Sodium / Q000172:deficiency* / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D004232:Diuretics; D012982:Sodium, Dietary; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D005665:Furosemide; D000803:Angiotensin I; D012964:Sodium; D019808:Losartan; D001920:Bradykinin; D009638:Norepinephrine